2.3  Anti-coronavirus activity of marine polysaccharides
Marine polysaccharides, such as carrageenan, PGS, chitosan, and their derivatives, show good inhibitory activity against various viruses, which provides a reference for their research on coronavirus. Iota-carrageenan containing lozenges show highly active against human rhinovirus (HRV), influenza virus A H1N1, and HCoV OC43 throughout the entire dissolution process, and are a promising therapy against viral infections of throat [67]. The cationically modified chitosan, N-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride (HTCC), shows significant inhibition against the human coronavirus HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1, and its hydrophobically modified derivative (HM-HTCC) is a potent inhibitor of the coronavirus HCoV-NL63, indicating that HTCC polymers based on chitosan are effective inhibitors of all low-pathogenic human coronaviruses [68]. Acute viral upper respiratory tract infection, also known as common cold, is mainly caused by respiratory viruses such as rhinovirus, coronavirus, influenza virus [[69], [70], [71]]. Clinical trials applying iota-carrageenan nasal spray have shown to reduce the duration of a virus-confirmed common cold. Carrageenan nasal spray shows significant antiviral efficacy in three virus subgroups, HRV, human coronavirus, and influenza A virus (IAV), and the highest effectiveness was observed in human corona virus-infected patients. The reduced duration of disease was 3 days (p < 0.01), and the number of relapses was three times less (p < 0.01) in carrageenan treated corona-virus -infected patients compared to control patients [70].
After the outbreak of SARS in 2003, many survivors developed residual pulmonary fibrosis with increased severity in older patients. Pulmonary fibrosis is caused by a hyperactive host response to lung injury mediated by epidermal growth factor receptor (EGFR) signaling in animal models (Fig. 5 ). Inhibition of EGFR signaling can prevent an excessive fibrotic response to SARS-CoV and other respiratory viral infections [72]. Moreover, sulfated polysaccharides such as fucoidan and sulfated rhamnan, can interfere or inhibit the expression and activation of EGFR pathway, which may help to suppress coronavirus [73,74]. The understanding of how polysaccharides play a role in EGFR and other pro-fibrotic pathways after viral infection will provide new ideas for COVID-19 treatment.
Fig. 5 The illustration about potential role of EGFR in lung fibrosis. Physical injury or a pathogen ① initiates the wound healing response by damaging healthy tissue, releasing EGFR ligands ② and activating the EGFR pathway. This results in an exaggerated wound healing response leading to a fibrotic lung ③. The early use of inhibitors like tyrosine kinase ④ could prevent the normal progress of wound healing and fibrosis [72].